After obtaining 80% cures of advanced tumors with Cytochlor/Cytofluor and 2 biomodulators, without side effects, in studies involving the radiation of 5 rodent tumors, the applicants conducted pilot studies with 5 human tumors in nude mice and achieved an average of 80% control of 1 glioblastoma, 1 lung, 1 breast and 2 prostate tumors. Their goals with 3 tumors: a) simplify the protocol with emphasis on CldC and H4U alone, b) compare: 1) slow release pellets with bolus doses, 2) CldC and IdU and BrdU (the first generation drugs), and 3) two radiosensitizers moving towards or in clinical trial. The end points will be days in tumor regrowth delay and number of cures. The applicants propose to determine a) the fraction of tumor cells containing CldU in their DNA, b) normal tissue damage to intestine, c) the capacity of CldC and FdC to restore silenced cad- cell lines to cad+ by hypomethylation. dCMP deaminase and dC kinase, enzymes which drive the selectivity of the technology, are elevated in many human tumors. The level of these enzymes in human tumor xenograftline and in human tumors and normal tissues will be examined with an emphasis of tumors of the head and neck and associated normal tissue from patients. PROPOSED COMMERCIAL APPLICATION: Radiation centers throughout the world which treat more than 60% of all cancer patients, are in search of a drug that will allow more aggressive treatment of cancer. The technology exploits the elevation of enzymes, important for success of the tumor, for a therapeutic advantage. The technology results in a 3-fold dose increase, so that cures with a real impact on survival can be obtained; e.g. a dose of 70 Gy will be as effective as a 210 Gy to the tumor without normal tissue damage. The world-wide patented invention will earn $60 million per year. The NCI has gound that the drug is not toxic to mice, dogs, and monkeys. Together with the cooperation of the NCI, we are about to launch a Phase I clinical trial with a simplified protocol utilizing only Cytochlor and one biomodulator.